Complications of immunosuppression
All immunosuppressive regimens used in organ transplantation increase the risk of infection and malignancy.
Transplant recipients receiving immunosuppressive therapy are at high risk from opportunistic infection, especially by viruses. Opportunistic infection is a potential problem in all transplant recipients, but those receiving aggressive immunosuppressive therapy after liver, heart, lung and small bowel transplantation are most at risk. Chemoprophylaxis is important in high-risk recipients.
The risk of bacterial infection is highest during the first month after transplantation. Transplant recipients are, like all patients undergoing major surgery, at risk of bacterial infections in the wound, respiratory tract and urinary tract. It is standard practice to give a broad-spectrum antibiotic to cover the perioperative period as prophylaxis against wound infection and possible bacterial contamination of the donor organ. The risk of bacterial infection is greatest in transplant recipients who are critically ill before or after surgery and are in the intensive care unit with indwelling catheters and lines. After recovery from surgery, the risk of bacterial infection is much reduced. Tuberculosis is a concern in patients who have previously had rnycobacterial infection and in patients from the Indian subcontinent, and it is usual to give immunochemoprophylaxis to these individuals for a period of 6—12 months after transplantation.
The risk of viral infection is highest during the first 6 months after transplantation and the most common problem is CMV infection. Most adults (> 80 per cent) develop CMV infection when they are children and have acquired immunity, as evidenced by the presence of IgG antibodies to CMV Following organ transplantation, CMV disease may arise because of reactivation of latent infection or because of primary infection that can be transmitted by an organ from a CMV-positive donor. The recipients at most risk from CMV infection are those who are CMV seronegative and receive an organ from a CMV-seropositive donor. Matching seronegative donors with seronegative recipients is an effective strategy for reducing the risk of CMV infection but is not very practicable. CMV disease typically presents with a high swinging fever, lethargy and leucopenia. The severity of the disease is variable and the clinical picture depends on the organ system most affected. It may present as:
• gastrointestinal disease;
Severe CMV disease is potentially fatal. Prophylaxis for CMV consists of passive immunisation using hyperimmune irnmunoglobulin or, more commonly now, administration of antiviral agents in the form of aciclovir or ganciclovir. A diagnosis of active CMV infection can be confirmed by serology, detection of CMV antigenaemia, CMV culture, PCR to detect viral DNA and histological examination of biopsy material. Treatment is with ganciclovir and is more effective when given pre-emptively on the basis of increased viral load as judged, for example, by quantitative PCR analysis for CMV
Herpes simplex virus (HSV) infection is common after transplantation and is usually due to reactivation of latent infection. It causes rnucocutaneus lesions around the mouth and sometimes the genitalia. These usually respond to topical treatment with acyclovir, but in severe cases systemic antiviral therapy is needed. Disseminated HSV infection is rare. Varicella zoster infection occurs more frequently in transplant patients and should be treated with systemic antiviral therapy.
Pneumocystis carinii is the most important protozoal infection after transplantation. It occurs during the first few months and presents with respiratory symptoms. The diagnosis is made by examination of bronchoalveolar lavage fluid or lung biopsy material for evidence of parasite infection. Prophylaxis with co-trimoxazole is highly effective and is usually continued for 6 months after transplantation.
Invasive fungal infections are uncommon in renal transplant recipients but infection with Candida or Aspergillus is more common after other types of solid organ transplantation. Fungal infection usually occurs in the first 3 months after transplantation, and early diagnosis and aggressive treatment are essential to avoid fatal infection.
After transplantation there is an increased risk of developing certain types of malignant disease, especially those turnouts where viral infection plays an aetiological role. The increased risk of malignancy is particularly high for skin cancer and non-Hodgkin’s lymphoma. Most of the skin cancers seen are squamous cell carcinomas, but basal cell carcinoma and malignant melanoma are also more common. The risk of skin cancer after transplantation rises with age and with exposure to sunlight, and it has been predicted that 50 per cent of transplant patients will develop a skin malignancy by 20 years. Patients must be warned of this risk before they undergo transplantation and advised to use an effective sun-screen. They should undergo regular review of their skin to detect malignancy and when such lesions occur they must be treated promptly and aggressively.
The risk of developing non-Hodgkin’s lymphoma is significantly increased after transplantation. This type of malignancy is classified as post-transplant lymphoproliferative disease (PTLD). Most of them are Epstein—Barr virus-induced B-cell turnouts. The overall risk of PILD is around 1 per cent per annum and is highest in patients who have received aggressive immunosuppression. PILD may occur in lymph nodes or at extranodal sites such as the gastrointestinal tract, lung, liver or in the transplanted organ. If PILD is identified at an early stage reduction or cessation of immunosuppressive therapy may cause disease regression and result in a cure. When advanced it is usually fatal. Both disseminated disease and central nervous system (CNS) involvement have a very poor prognosis.
Transplant patients also have a 300-fold increased risk of developing Kaposi’s sarcoma, although this malignancy is still very uncommon after transplantation.
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